Smartphone-based multispectral dermascope

ABSTRACT

Methods, apparatus and systems that relate to a portable multispectral dermascope are described. An example dermascope includes light sources having different spectral contents and configured to illuminate an area of the skin and at least one imaging sensor configured to collect light that it receives from the area of the skin. The dermascope also includes a processor to control illumination provided by the light sources to the area of the skin and process information associated with received light from the area of the skin to produce images of the area of the skin. In the dermascope, illumination from the light sources is controlled to provide illumination in a plurality of distinct wavelengths or range of wavelengths that produce differing optical responses of the area of the skin. The described methods and devices can be used to identify skin conditions using a compact and convenient device, such as a mobile phone.

RELATED APPLICATIONS

This patent document claims priority to and benefits of U.S. ProvisionalPatent Application No. 63/090,102 entitled “SMARTPHONE-BASEDMULTISPECTRAL DERMASCOPE” and filed on Oct. 9, 2020. The entire contentsof the before-mentioned patent application are incorporated by referenceas part of the disclosure of this patent document.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

This invention was made with government support under Grant No.EB000809, and Grant No. OD018061, awarded by the National Institutes ofHealth. The government has certain rights in the invention.

TECHNICAL FIELD

The disclosed technology relates generally to optical methods anddevices which can facilitate identification of various skin conditionsand, more specifically, to portable dermascope devices in someembodiments.

BACKGROUND

Dermoscopy is an in vivo technique which is primarily used for theexamination of pigmented skin lesions. Dermoscopy can be used todifferentiate between benign and malignant lesions. Currently,dermascopes and their accessories range from hundreds to thousands ofdollars in price, which is potentially too expensive for general medicalpractices. Accordingly, there is still a need to produce a low-costhand-held dermascope device.

SUMMARY OF CERTAIN EMBODIMENTS

The techniques disclosed herein can be implemented in variousembodiments to achieve a portable (e.g., a mobile device based)multispectral dermascope.

An aspect of the disclosed embodiments relates to a dermascope forimaging an area of a skin that includes a plurality of light sourceshaving different spectral contents and configured to illuminate the areaof the skin. The dermascope further includes at least one imaging sensorconfigured to collect images of the area of the skin. The dermascopealso includes a processor and a memory comprising instructions storedthereon, wherein the instructions upon execution by the processor, causethe processor to control illumination provided by the plurality of lightsources to the area of the skin, and process information associated withthe images produced from reflected light from the area of the skin toenable detection of a level of one or more chromophores in the skin,wherein illumination from the plurality of light sources is controlledto provide illumination in a plurality of distinct wavelengths or rangeof wavelengths where the one or more chromophores exhibit differingoptical characteristics.

Another aspect of the disclosed embodiments relates to a method ofimaging an area of a skin to determine a content of at least onechromophore in the skin that includes illuminating the area of the skinusing a plurality of light sources having distinct spectral content toprovide illumination in a plurality of distinct wavelengths or range ofwavelengths where deoxyhemoglobin, oxyhemoglobin, or melanin exhibitdiffering optical characteristics. The method also includes obtainingone or more images of the area of the skin. The method further includesprocessing information associated with the one or more images to obtaina level of at least one chromophore in the skin.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1(a)-1(e) illustrate two smartphone-based dermascope systemconfigurations in accordance with example embodiments.

FIG. 2 illustrates a layout of a smartphone camera and an achromat whichis part of an auxiliary optical system at the front end of a smartphonein accordance with an example embodiment.

FIG. 3 illustrates example molar extinction coefficients, ε(λ), foroxyhemoglobin, deoxyhemoglobin and melanin as well as light-emittingdiode (LED) spectral flux probability density functions, ϕ_(e,λ),according to the present disclosure.

FIG. 4(a) illustrates an electronics block diagram of a dermascopesystem according to an example embodiment.

FIGS. 4(b) and 4(c) illustrate screenshots of an Android applicationaccording to an example embodiment.

FIG. 5 illustrates example color matching curves which can be used todetermine normalization constants to convert to CIELAB color space alongwith the 4000 K white-LED spectrum.

FIGS. 6(a)-6(f) illustrate RGB, chromophore, melanin, and erythemameasures for a case of junctional nevus (JN) obtained using a USB cameradermascope and a smartphone camera dermascope according to the disclosedtechnology.

FIGS. 7(a)-7(f) illustrate RGB, chromophore, melanin, and erythemameasures for a case of squamous cell carcinoma (SCC) obtained using aUSB camera dermascope and a smartphone camera dermascope according tothe present disclosure.

FIG. 8 illustrates chromophore maps for an example embodiment of a USBcamera dermascope and an example embodiment of a smartphone cameradermascope at certain time points during an occlusion test.

FIG. 9 shows changes in a mean of a sum of the red, green, and blueimage channels over varying exposure times for an example embodiment ofa smartphone camera based dermascope and over brightness settings for anexample embodiment of a USB camera based dermascope.

FIGS. 10(a)-10(f) show full-field and zoomed 1951 USAF resolution testchart images after cropping along with modulation transfer function(MTF) data measured using the slanted-edge test for a smartphone camerabased dermascope and a USB camera based dermascope according to thepresent disclosure.

FIG. 11 shows example maps of illumination uniformities for a smartphonecamera based dermascope and a USB camera based dermascope according tothe disclosed technology.

FIG. 12 show a flow diagram of an example embodiment of a method ofprocessing reference images according to an example embodiment.

FIG. 13 show a flow diagram of an example embodiment of a method ofprocessing white-light images according to another example embodiment.

FIG. 14 show a flow diagram of an example embodiment of a method ofprocessing multispectral images according to an example embodiment.

FIG. 15 illustrates example finger occlusion test results for asmartphone camera a USB camera.

FIG. 16 shows a dermascope according to an example embodiment.

FIG. 17 shows a flow diagram of an example embodiment of a methodaccording to the disclosed technology.

FIG. 18 shows a set of operations for imaging an area of a skinfacilitate a determination of a skin condition in accordance with anexample embodiment.

DETAILED DESCRIPTION

The techniques disclosed herein overcome the shortcomings of priorsystems and can be implemented in various embodiments to provide alow-cost handheld dermascope. The disclosed devices and systems, amongother features and benefits, address the need for low-cost, handheldimaging systems that can be used for detecting and diagnosing skinconditions such as, e.g., melanoma or erythema.

The rates of melanoma and nonmelanoma skin cancers (NMSC) have beensteadily rising, and early diagnosis is key for improved outcomes.Because there is a shortage of board-certified dermatologists,particularly in remote or underserved settings where <10% ofdermatologists practice, most of the burden of diagnosis and treatmentfalls on primary care physicians (PCPs) who are not extensively trainedin dermatological care. Dermoscopy is a tool utilized to improve the invivo diagnostic accuracy of benign versus malignant lesions, a uniqueskill that requires additional training, even among board-certifieddermatologists. In remote settings, dermascopes may capture and documentpigmented lesions that can be forwarded to expert colleagues throughtelemedicine for further analysis. Unfortunately, dermascopes and theiraccessories range from hundreds to thousands of dollars, which ispotentially too expensive for general medical practice. Thus, there is aneed for a low-cost, readily available dermoscopy tool to bridge thisclinical need.

Lesion evaluation using visual, subjective methods such as the ABCDEcriteria and seven-point checklist are useful tools for PCPs. The ABCDEcriteria predict melanoma by a lesion's asymmetry, border irregularity,coloration, diameter if >6 mm, and evolution, providing a sensitivity of0.85 and specificity of 0.72. The seven-point checklist monitors alesion's change in size, shape, color, and looks for diameters >7 mm,crusting or bleeding and sensory change, providing a sensitivity of 0.77and specificity of 0.80. Continuous monitoring has shown to improveoutcomes through early detection as evidenced by mole mapping techniquesand the increase in sensitivity and specificity with the addition of theevolving in the ABCDE criteria.

Adjunctive tools utilizing objective measures such as polarizedmultispectral imaging (PMSI) and polarized white-light imaging (PWLI) tomap dermal chromophores (e.g., hemoglobin, oxyhemoglobin (HbO₂),deoxyhemoglobin (Hb), and/or melanin), quantify erythema, and performimage classification for lesion screening have the potential to increaseearly detection of melanoma by PCPs and even outside the physician'soffice, leading to reduced need for biopsy and improved outcomes.Disclosed herein are systems and devices that utilize a mobileelectronic device (e.g., a smartphone, a tablet, or the like) combinedwith LED illumination as the platform for an adjunctive medical device.The disclosed devices provide a portable system with easy-to-operateapps and native image capture, processing and data transmissioncapabilities. These systems can reduce the costs associated withinterference-filter-based or spectrometer-based systems while alsoproviding a more compact, portable geometry for use in any testingenvironment compared with clinical-grade imaging systems.

Disclosed herein are two example point-of-care dermascope configurationsfor skin lesion screening and erythema monitoring, implementing bothPMSI and PWLI on an LG G5 (LG, Seoul, South Korea) smartphone platform.These configurations are provided by the way of example, and not bylimitation, to illustrate the principles of operation of the discloseddermascope. One example system utilizes the embedded smartphone camerafor imaging while the other example system uses a USB-connected cameramodule that connects to the smartphone. Both systems share a commonillumination system and software application to enable PWLI and PMSI.

Two example PMSI and PWLI dermascope systems which use the smartphone'sembedded rear camera are shown in FIGS. 1(c)-1(e). The main LG G5 camera(170 in FIGS. 1(c) and 1(e)) includes a Sony IMX234 Exmor RS sensor with5312×2988, 1.12-μm pixels and a 5.95 mm×3.35 mm sensor size. The sensoris paired with a ƒ/1.8, 4.42-mm focal length lens.

To decrease the working distance of the optical system to allow imagingof the epidermis, a 24-mm focal length achromatic doublet (180 in FIG.1(d); Ross Optical, El Paso, Texas, USA) is placed 4 mm away from theprincipal plane of the smartphone optical system, providing amagnification of m=0.187 and a numerical aperture NA=0.04. Aftercropping the field of view (FOV) is 9.96 mm×11.67 mm, as shown in FIG. 2. It should be noted that the configuration of FIG. 2 is only providedas an example, and other auxiliary optical systems can be designed andconstructed to provide the desired FOV, numerical apertures,magnification, zoom capability and/or working distance for theparticular electronic mobile device and/or for different applicationsthat may have particular imaging requirements. As shown in FIG. 2 , theimaging achromat 205 (which can be part of the auxiliary optical system210) can be aligned to the smartphone camera (220 in FIG. 2 ) using, forexample, a machined poly(methyl methacrylate) (PMMA) disk (115 in FIG.1(c)) installed in a removable 3D-printed annulus (110 in FIG. 1(c))made of, e.g., VeroBlue RGD840 (Stratasys, Eden Prairie, Minnesota, USA)plastic. The annulus 110 (see, e.g., FIGS. 1(a) and 1(c)) serves as animaging guide. Its length can equal to the optical system workingdistance (23 mm), so the PCP can contact the patient to stabilize thedevice and ensure correct focus. An additional 3D-printed structure (117in FIG. 1(d)) serves as a mounting platform for the smartphone (e.g.,smartphone 190 shown in FIG. 1(e)), imaging annulus, and LED electronics(e.g., illumination LED printed circuit board (PCB) 120 shown in FIGS.1(a) and 1(c)). In some implementations, a transparent piece of glass orplastic can be placed at the end of the annulus to flatten the skin(e.g., in the non-3D mode) to make the object plane (the skin) flat forbetter imaging. This feature can also facilitate the sterilization ofthe device. It should be noted that the auxiliary optical system caninclude mirrors, metasurfaces, metalenses, or diffractive optics toobtain the desired performance characteristics.

An alternative PMSI and PWLI dermascope example configurationillustrated in FIGS. 1(a) and 1(b) is also based on an LG smartphoneplatform, but it utilizes an external USB-connected RGB camera 150(e.g., OV5648, Omnivision, Santa Clara, California, USA; 5 MP, 3.67mm×2.74 mm) with the vendor-supplied ˜2.8-mm focal length lens adjustedto a working distance of 30 mm. The camera 150 shown in FIG. 1(a) can beconnected to a smartphone using, e.g., a USB cable 160 shown in FIG.1(b). After cropping, the FOV is 27.5 mm×20 mm. In addition, theintegrated infrared (IR) filter of the camera 150 was removed to allowillumination and capture of IR light that can be particularly beneficialfor skin imaging Again, the mechanical design of the annulus is matchedto the working distance of the camera, providing in-focus imaging whenthe device contacts the patient.

As noted above, FIGS. 1(a)-1(e) illustrate two example dermascopeimplementations. The USB-camera-based PMSI and PWLI dermascope is shownin FIGS. 1(a) and 1(b). FIG. 1(a) illustrates various components of thehandheld imaging module (the USB camera 150 is hidden behind the imagingpolarizer 140). FIG. 1(b) illustrates the imaging module paired with thesmartphone camera. LEDs are positioned on the illumination LED PCB 120to provide illumination toward the skin (toward the open end of theannulus). A Polarization filter (e.g, the illumination polarizer 130shown in FIGS. 1(a) and 1(c)) can be positioned in front the lightsources to produce polarized light having a particular polarizationstate. Upon reflection from the skin, the reflected light is receivedand collected by the camera lens. Another polarization filter (e.g., theimaging polarizer 140 shown in FIGS. 1(a) and 1(c)) can be placed inpath of the reflected light to reduce stray light contamination. Theimage data (or associated electrical signals) corresponding to theimages is received at the smartphone, and is stored, processed and/ortransmitted to a remote device for processing/storage.

An example smartphone-camera-based PMSI and PWLI dermascope is shown inFIGS. 1(c)-1(e). FIG. 1(c) illustrates the smartphone-based dermascopesystem's side opposite the smartphone screen with the imaging annulus110 removed, where the LED PCB 120 and smartphone camera 170 are visibleand other components are highlighted. FIG. 1(d) illustrates thedermascope system with the imaging annulus attached. FIG. 1(e)illustrates the smartphone installed in the dermascope.

FIG. 2 illustrates a layout of a smartphone camera 220 (e.g., a cameraof an LG G5 smartphone) and an achromat 205 which is part of anauxiliary optical system 210 at the front end of the smartphone,according to an example embodiment. The smartphone camera lens systemcan be modeled as a paraxial lens, which simplifies the design of thefront-end system.

For both example dermascope systems illustrated in FIGS. 1(a)-1(e),multispectral illumination can be accomplished using a custom printedcircuit board (e.g., the board 120 shown in FIGS. 1(a) and 1(c)) withLEDs of various wavelengths (e.g., Lumileds, Amsterdam, The Netherlandsor Vishay, Malvern, Pennsylvania, USA) installed as, e.g., shown inTable 1. In some example embodiments, the color wavelengths can bechosen based on the ability to probe both hemoglobin isosbestic pointsand separate oxygenated from deoxygenated hemoglobin content along themolar attenuation curves (FIG. 3 ).

According to some example embodiments of the smartphone-baseddermascope, the PMMA disk 115 used for mounting a lens (e.g., theimaging achromat 180 shown in FIG. 1(d)) or, more generally, formounting the auxiliary optical system 210 also extends over theillumination LEDs to provide mounting for a polarizer (e.g., a linearpolarizer; Edmund Optics, Barrington, New Jersey, USA) such as theillumination polarizer 130 shown in FIGS. 1(a) and 1(c). An orthogonallinear polarizer (e.g., the imaging polarizer 140) can be installed infront of the imaging channel, enabling both PMSI and PWLI and reducingthe effect of specular reflection on the images. The LED sources'spectral fluxes, ϕ_(e,λ), shown in the lower panel in FIG. 3 , weremeasured with a spectrometer (Ocean Optics).

The example USB-camera-based dermascope illustrated in FIGS. 1(a)-1(b)uses the same LED PCB 120 and wavelengths for illumination along withorthogonal polarizers in the illumination channel (130; Edmund Optics)and the imaging channel (140; Moxtek, Orem, Utah, USA). In some exampleembodiments, to help normalize white-light image luminance, an 18% graycolor reference (e.g., Kodak, Rochester, New York, USA) can be installedon both sides of the image FOV. Because the 3D-printed mountingfoundation does not need to mount the LED board and imaging annulus, apreviously designed geometry is used for this system.

Table 1 provides a listing of LED and camera settings for eachillumination wavelength and each dermascope. LED wavelength (λ), LEDpart number, smartphone camera LED-driving current (l), smartphonecamera LED flux for a single LED of the given color, smartphone cameraInternational Organization for Standardization setting, smartphonecamera exposure time, USB camera LED-driving current (l), USB camera LEDflux for a single LED of the given color, USB camera brightness setting,and USB exposure time are provided.

TABLE 1 Smartphone camera settings USB camera settings Exposure Exposureλ (nm) Part number /(mA) Flux ISO time (ms) /(mA) Flux Brightness time(ms) 4000K LXZ1-4070 358 101 lm 100 3.8 620 161 lm 50 1.6 450 LXZ1-PR01620 690 mW 100 0.5 620 690 mW 50 1.6 470 LXZ1-PB01 620 46 lm 100 0.7 62046 lm 50 1.6 500 LXZ1-PE01 620 100 lm 100 2.6 620 100 lm 50 1.6 530LXZ1-PM01 620 142 lm 100 3.0 620 142 lm 50 1.6 580 LXZ1-PL01 358 42 lm100 5.0 620 67 lm 50 1.6 660 LXZ1-PA01 620 420 mW 100 0.9 620 420 mW 501.6 810 VSMY98145DS 620 700 mW 2390 250.0 620 700 mW 50 1.6 940L1IZ-0940 358 403 mW 2300 180.0 620 700 mW 50 1.6

FIG. 3 illustrates molar extinction coefficients, ε(λ), for Hb, HbO₂,and melanin plotted on a log scale in the upper panel and, as mentionedearlier, the LED spectral flux probability density functions, ϕ_(e,λ),plotted on a linear scale in the lower panel.

In the example dermascope systems shown in FIGS. 1(a)-1(e), theillumination LED PCB 120 includes three LEDs of each color (e.g., red,green, blue) soldered in a symmetrical pattern around the cameraaperture to maximize uniformity without additional beam shaping optics.The backside solder mask of the PCB was removed to expose the copper andis attached to a copper heatsink with electrically insulating epoxy(DP240, 3M, St. Paul, Minnesota, USA). Numerous vias were placed on thePCB to ensure a low thermal resistance between the front and backsidecopper planes. The LEDs are driven with a switching boost power supply(LT3478, Linear Technology, Milpitas, California, USA) powered by twolithium-ion batteries (Orbtronic, Saint Petersburg, Florida, USA). EachLED color string can be turned on individually with a custom power levelsetting and/or illumination setting and synchronized with the imagecapture by, e.g., an Android application (also referred to as app)through, e.g, a Bluetooth-connected microcontroller (MCU, IOIO-OTG,SparkFun Electronics, Niwot, Colorado, USA). The intensity of light canbe controlled, for example, by adjusting the illumination output of eachof the plurality of LEDs (e.g., each of the three LEDs of the samecolor) individually or collectively. Example LED-driving currents,fluxes, and dermascopes' image capture settings are shown in Table 1. Inaddition, the smartphone camera (e.g., 170 in FIGS. 1(c) and 1(e)) orthe USB camera 150 (FIG. 1(a)) can use the daylight white balancesetting.

A block diagram of an example implementation of the dermascope systemelectronics is shown in FIG. 4 . For both the USB camera and theon-board smartphone camera based dermascope systems, the Androidapplication running, e.g., on the smartphone (e.g., smartphone 190 shownin FIG. 1(e)) can be configured to control the camera functions, controlcamera synchronization with the LED illumination, and set cameraexposure time. Images captured by the camera of the dermascope systemcan be associated with an ID assigned to each patient, thus removing theneed to store identifiable information related to the patient on thesmartphone. Example screenshots of the Android app are shown in FIGS.4(a)-4(c).

FIG. 4(a) illustrates an electronics block diagram of a dermascopesystem according to an example embodiment. FIGS. 4(b) and 4(c)illustrate Android application screenshots. Below, operational steps,data collection methods and/or algorithms, and other operations relatedto the dermascope systems according to the present disclosure aredescribed by the way of example.

Different algorithms can be used to process collected dermal images. Twoexample algorithms are provided in Algorithms 1 and 2 at the end of thispatent document. Descriptions of the steps and related equations areprovided below.

In some implementations, reference images can be collected to allowproper calibration of image parameters for later-captured images. Forexample, in an example implementation, images of a reflective gray card(e.g., 18% reflectivity) can be collected by a dermascope systemaccording to the disclosed technology at one or more wavelengths toserve as both the optical density (OD) and illumination uniformityreferences.

For dermal image collection, a pilot study was performed on humansubjects at the University of Arizona College of Medicine, Division ofDermatology to determine feasibility of each multi-spectral dermascope.This study received institutional review board approval (#1612067061).All patients provided informed written and oral consent.

The melanin content, erythema, and chromophore concentrationmeasurements rely on conversion to the CIELAB and CIEXYZ color spaces.The imaging systems natively capture in the sRGB color space, and theimages are first converted to linear RGB space:

$\begin{matrix}{C_{linear} = \left\{ {\begin{matrix}\frac{C_{sRGB}}{12.92} & {C_{sRGB} \leq 0.04045} \\\left( \frac{C_{sRGB} + 0.055}{1 + 0.055} \right)^{2.4} & {C_{sRGB} > 0.04045}\end{matrix},} \right.} & (1)\end{matrix}$

where C_(sRGB) is each channel of the I_(sRGB) image. Images are thenconverted from RGB_(linear) to CIEXYZ using the transformation matrix,

$\begin{matrix}{{\begin{bmatrix}X \\Y \\Z\end{bmatrix} = {\begin{bmatrix}0.4124 & 0.3576 & 0.1805 \\0.2126 & 0.7152 & 0.0722 \\0.0193 & 0.1192 & 0.9505\end{bmatrix} \cdot \begin{bmatrix}R_{linear} \\G_{linear} \\B_{linear}\end{bmatrix}}},} & (2)\end{matrix}$

where Y is the luminance value and is used to calculate ODs from thedermis images and reference. Luminance is a measure that scales opticalradiation by the response of the human visual system. Because the imageswill be processed by a computer, accurate color representation for ahuman is not required, so an additional luminance measure, Y_(equal), iscreated using the equal sum of all three channels:

$\begin{matrix}{\left\lbrack Y_{equal} \right\rbrack = {\lbrack 111\rbrack \cdot {\begin{bmatrix}R_{linear} \\G_{linear} \\B_{linear}\end{bmatrix}.}}} & (3)\end{matrix}$

Using the reference images that have been converted to CIEXYZ or Yequal,reference luminance images are defined as

I₀=Y_(ref) ,   (4)

where Y_(ref) is the Y (luminance) channel of the CIEXYZ image orY_(equal). The reference gray scale image is normalized to serve as theillumination reference for the dermal images.

$\begin{matrix}{{U = \frac{Y_{ref}}{\max\left( Y_{ref} \right)}},} & (5)\end{matrix}$

where U is now the illumination uniformity correction matrix.

The dermal CIEXYZ and Yequal images are corrected in the same way

$\begin{matrix}{{I_{{dermal},{{uniformity}{corrected}}} = {\frac{I_{dermal}}{U}\overset{\_}{U}}},} & (6)\end{matrix}$

where I_(dermal) is the illumination uniformity corrected dermal imagewith constant mean luminance. Finally, OD dermal images are calculatedas

$\begin{matrix}{{OD} = {- {{\ln\left( \frac{I}{I_{0}} \right)}.}}} & (7)\end{matrix}$

In some example embodiments, a USB dermascope can have sections of a 18%gray photography card mounted on either side of the FOV (e.g., elements111 and 112 in FIG. 1(b)). Knowing the card image should equal 50%levels of RGB, the luminance of the white-light image can be scaledusing the following equation:

$\begin{matrix}{I_{{dermal},{{luminance}{corrected}}} = {I_{{dermal},{{uniformity}{corrected}}}{\frac{0.5}{\overset{\_}{Y_{gray}}}.}}} & (8)\end{matrix}$

The Beer-Lambert law can be utilized to measure the relativeconcentrations of Hb, oxyhemoglobin (HbO2), and melanin:

I(λ)=I ₀(λ)exp[−c _(n)ε(λ)

(λ)],   (9)

where I is the resulting intensity, I₀ is the incident intensity, c_(n)is the concentration of the chromophore, ε(λ) is the molar attenuationcoefficient of the chromophore at a particular wavelength, and

(λ) is the optical path length of the light in the medium for theincident wavelength. This can be restated as OD:

$\begin{matrix}{{{OD} = {{- {\log\left( \frac{I(\lambda)}{I_{0}(\lambda)} \right)}} = {{c_{Hb}{\varepsilon_{Hb}(\lambda)}{\ell(\lambda)}} + {c_{{HbO}_{2}}{\varepsilon_{{HbO}_{2}}(\lambda)}{\ell(\lambda)}} + c_{melanin} + {{\varepsilon_{melanin}(\lambda)}{\ell(\lambda)}} + c_{background}}}},} & (10)\end{matrix}$

where c_(background) is due to residual absorption from moleculespresent in the epidermis and dermis.

The molar extinction coefficients for Hb and HbO₂ and melanin are shownin FIG. 3 . Jacques's ε_(melanin) was fit with an exponential curve toextend the wavelength to 1000 nm, resulting in a fit of

ε_(melanin)=2.2858·10⁴exp(−5.5028·10⁻³λ).   (11)

Optical path lengths,

(λ), for the chromophores can be calculated from a linear fit ofAnderson's data in the region of the illumination wavelengths,

(λ)=2.62·10⁻⁴λ−9.87·10⁻²,   (12)

where λ is in units of nm and

(λ) is in units of cm.

Because the LEDs are broad spectrum, we can integrate over thewavelength probability density function to calculate a total molarattenuation coefficient for each color

ε_(total)=∫ϕ_(e,λ)(λ)ε(λ)dλ.   (13)

The resulting molar attenuation coefficients for the Hb, HbO_(2,) andmelanin chromophores are shown in Table 2.

TABLE 2 Molar extinction coefficients calculated using Eq. (13) for eachillumination wavelength compared with the molar extinction coefficientsfor the peak wavelength. Coefficients at peak LED Coefficients from Eq.(13) wavelength Wave- Hb HbO₂ Melanin Hb HbO₂ Melanin length (cm⁻¹ (cm⁻¹(cm⁻¹ (cm⁻¹ (cm⁻¹ (cm⁻¹ (nm) M⁻¹) M⁻¹) M⁻¹) M⁻¹) M⁻¹) M⁻¹) 450 199,86482,747 1922 103,292 62,816 1921 470 35,937 36,662 1706 16,156 33,2091721 500 26,659 25,521 1392 20,862 20,932 1459 530 37,824 34,851 124139,036 39,957 1237 580 22,606 13,258 869 37,010 50,104 940 660 3380 352611 3227 320 605 810 845 812 281 717 864 265 940 656 1185 142 693 1214130

A system of equations is built from the multispectral datacube and themolar attenuation coefficients shown in Table 2

$\begin{matrix}{{\left\lbrack \text{⁠}\begin{matrix}{{\varepsilon_{Hb}\left( \lambda_{1} \right)}{\ell\left( \lambda_{1} \right)}} & {{\varepsilon_{{HbO}_{2}}\left( \lambda_{1} \right)}{\ell\left( \lambda_{1} \right)}} & {{\varepsilon_{melanin}\left( \lambda_{1} \right)}{\ell\left( \lambda_{1} \right)}} & 1 \\{\varepsilon_{Hb}\left( \lambda_{2} \right)\ell\left( \lambda_{2} \right)} & {\varepsilon_{{HbO}_{2}}\left( \lambda_{2} \right)\ell\left( \lambda_{2} \right)} & {\varepsilon_{melanin}\left( \lambda_{2} \right)\ell\left( \lambda_{2} \right)} & 1 \\{\varepsilon_{Hb}\left( \lambda_{3} \right)\ell\left( \lambda_{3} \right)} & {\varepsilon_{{HbO}_{2}}\left( \lambda_{3} \right)\ell\left( \lambda_{3} \right)} & {\varepsilon_{melanin}\left( \lambda_{3} \right)\ell\left( \lambda_{3} \right)} & 1 \\ \vdots & \vdots & \vdots & \vdots \\{\varepsilon_{Hb}\left( \lambda_{n} \right)\ell\left( \lambda_{n} \right)} & {\varepsilon_{{HbO}_{2}}\left( \lambda_{n} \right)\ell\left( \lambda_{n} \right)} & {\varepsilon_{melanin}\left( \lambda_{n} \right)\ell\left( \lambda_{n} \right)} & 1\end{matrix} \right\rbrack\left\lbrack \text{⁠}\begin{matrix}c_{Hb} \\c_{{HbO}_{2}} \\c_{melanin} \\c_{background}\end{matrix} \right\rbrack} = {{\left\lbrack \text{⁠}\begin{matrix}{{OD}\left( \lambda_{1} \right)} \\{{OD}\left( \lambda_{2} \right)} \\{{OD}\left( \lambda_{3} \right)} \\ \vdots \\{{OD}\left( \lambda_{n} \right)}\end{matrix} \right\rbrack.}}} & (14)\end{matrix}$

and the system is solved by linear algebra least-squares techniqueswhere OD(λ_(n)) are calculated OD matrices for each illuminationwavelength.

The ability of the dermascopes according to the present disclosure toproperly measure relative chromophore concentrations was validated usinga finger occlusion test. Images were taken with both dermascopesillustrated in FIGS. 1(a)-1(e) and the chromophores were mappedpreocclusion, after 2 min of occlusion, postocclusion, and 5 min afterending the occlusion.

To measure melanin content and erythema, the white-light image can beconverted to the CIELAB color space using lightness (L*) as a measure ofrelative melanin content and the direction of red color stimuli (a*) asa measure of redness, with more positive values indicating higher levelsof erythema. Before converting to CIELAB, normalization constants can becalculated from the white-LED spectral content. Using the color matchingfunctions, x(λ), y(λ), z(λ) (FIG. 5 ), X, Y, and Z can be calculated as

X=∫ _(380 nm) ^(780 nm) x (λ)ϕ_(e,λ) dλ; Y=∫ _(380 nm) ^(780 nm) y(λ)ϕ_(e,λ) dλ; Z=∫ _(380 nm) ^(780 nm) z (λ)ϕ_(e,λ) dλ,   (15)

where ϕ_(e,λ) is the relative spectral flux of the white-LED source asshown in FIG. 3 . The normalization constants X_(n), Y_(n), and Z_(n)can be calculated as

$\begin{matrix}{{X_{n} = \frac{X}{Y}};{Y_{n} = \frac{Y}{Y}};{Z_{n}{\frac{Z}{Y}.}}} & (16)\end{matrix}$

The image can be then converted to CIELAB by

$\begin{matrix}{{{L^{*}116{f\left( \frac{Y}{Y_{n}} \right)}} - 16},{a^{*} = {500\left\lbrack {{f\left( \frac{X}{X_{n}} \right)} - {f\left( \frac{Y}{Y_{n}} \right)}} \right\rbrack}},{b^{*} = {200\left\lbrack {{f\left( \frac{Y}{Y_{n}} \right)} - {f\left( \frac{Z}{Z_{n}} \right)}} \right\rbrack}},} & (17)\end{matrix}$ where $\begin{matrix}{{f(x)} = \left\{ {\begin{matrix}x^{1/3} & {x > \left( {24/116} \right)^{3}} \\{{\left( {841/108} \right)x} + {16/116}} & {x \leq \left( {24/116} \right)^{3}}\end{matrix}.} \right.} & (18)\end{matrix}$

FIG. 5 illustrates color matching curves used to determine normalizationconstants to convert to CIELAB along with the 4000 K white-LED spectrum.

In addition to the white-light image measures, melanin and erythemameasures can be constructed from the color-OD images. Melanin contentcan be calculated as

Melanin=OD ₆₆₀ −OD ₉₄₀.   (19)

As shown in Table 2, these two wavelengths maximize the difference inmelanin absorption and minimize the effect of Hb and HbO₂ absorption.

Erythema, due to increased blood content, results in increased bluelight absorption but little change in red light absorption as shown inTable 2. Therefore, an erythema index can be constructed as

Erythema=OD ₄₇₀ −OD ₆₆₀.   (20)

The linearity of the camera responses was measured by adjusting theexposure time in the case of the smartphone-camera-based dermascope andimage brightness in the case of the USB-camera-based dermascope,capturing images of the matte 18% gray photography card with each LEDcolor, and measuring the image luminance mean at each wavelength.

Performance of the imaging system's cutoff frequency and FOV wasvalidated with a 1951 United States Air Force (USAF) resolution testchart, and the modulation transfer function (MTF) was measured using theslanted-edge method.

Illumination uniformity was measured by illuminating the matte 18% grayphotography card with each LED color and imaging the surface of the cardwith the dermascope. The uniformity is quantified using the coefficientof variation, (c_(v)), on normalized data

$\begin{matrix}{{{Uniformity} = {{1 - c_{v}} = {1 - \frac{\sigma}{\overset{\_}{x}}}}},} & (21)\end{matrix}$

where x is the mean of the pixels in the image and σ is the standarddeviation of the pixel values.

RGB, chromophore, melanin, and erythema measures for cases of junctionalnevus (JN) and squamous cell carcinoma (SCC) are shown in FIGS. 6 and 7, respectively. Each case was captured with both the USB cameradermascope and the smartphone camera dermascope.

The chromophore maps for both dermascopes at the chosen time points forthe occlusion test are shown in FIG. 8 .

FIG. 9 shows the changes in the mean of the sum of the red, green, andblue image channels over varying exposure times for the smartphonecamera based dermascope and over brightness settings for the USB camerabased dermascope.

FIG. 10 shows full-field and zoomed 1951 USAF resolution test chartimages after cropping along with MTF data measured using theslanted-edge test for both dermascopes.

Maps of the illumination uniformities of both systems are shown in FIG.11 , and the coefficients of variations are given in Table 3.

The CIEXYZ normalization constants calculated from the white-LEDspectrum for the two dermascopes (a smartphone camera based dermascopeand a USB camera based dermascope according to the present disclosure)are shown in Table 4.

FIGS. 6(a)-6(f) illustrate the same JN imaged by both the smartphone andUSB dermascopes. For the smartphone dermascope, FIG. 6(a) illustratesthe RGB images after illumination uniformity correction, FIG. 6(b)illustrates the relative chromophore concentrations, and FIG. 6(d)illustrates lightness as measured by L*, redness as measured by a*,melanin calculated from Eq. (19), and erythema calculated from Eq. (20).The same measures are shown for the USB dermascope in FIGS. 6(f), 6(c),and 6(e), respectively. A 5-mm scale bar is provided for both thesmartphone-camera images and the USB camera images above the RGB imagegrids.

FIGS. 7(a)-7(f) illustrate the same SCC imaged by both the smartphoneand USB dermascopes. For the smartphone dermascope, FIG. 7(a)illustrates the RGB images after illumination uniformity correction,FIG. 7(b) illustrates the relative chromophore concentrations, and FIG.7(d) illustrates lightness as measured by L*, redness as measured by a*,melanin calculated from Eq. (19), and erythema calculated from Eq. (20).The same measures are shown for the USB dermascope in FIGS. 7(f), 7(c),and 7(e), respectively. A 5-mm scale bar is provided for both thesmartphone-camera images and the USB camera images above the RGB imagegrids.

The distribution of polarized multispectral dermascopes according to thedisclosed technology which are based on smartphone platforms andlow-cost color LEDs to PCPs (and eventually to consumers) has thepotential to democratize dermal chromophore and melanoma mapping alongwith erythema monitoring, improving quantitative monitoring of lesionsand increasing early detection of skin cancers.

These smartphone based platforms demonstrate a number of advantagescompared with previous systems targeting chromophore mapping and skincancer screening. The smartphone based dermascope platform according tothe disclosed technology is a compact, low-cost, portable, easy-to-usesystem with native image capture and processing capabilities, whichremoves the need for expensive, clinical-grade imaging systems. Theplatform is flexible enough to use either the camera embedded in amobile device (e.g., a smartphone or a tablet) for imaging or a separateUSB camera connected to the mobile device, depending on the desiredergonomics of the user. Both system implementations can still use thebuilt-in smartphone camera for wide-field, white-light, and dermalimaging (e.g., the annulus 110 in FIG. 1(c) can be removed).Additionally, the smartphone camera can be used for large area imagecapture either using the smartphone-camera-based dermascope with theimaging annulus removed or using the USB camera's host smartphone.

FIG. 8 illustrates finger occlusion test results for the smartphonecamera and USB camera at preocclusion, after occlusion for 2 min, andpostocclusion. The bottom plot in FIG. 8 provides the mean relativeconcentration for Hb and HbO₂ inside the rectangle showing a dip in HbO₂and increase in Hb after occlusion.

FIG. 9 illustrates mean of the sum of the red, green, and blue channelsover changing exposure times for the smartphone camera based dermascopeand changing brightness settings for the USB camera based dermascope.

FIGS. 10(a)-10(c) illustrate smartphone camera and FIGS. 10(d)-10(f)illustrate USB camera results of 1951 USAF resolution test chart imagingalong with measured MTFs from a slanted-edge test. The smartphonecamera's measured MTF matches the USAF cutoff frequency of group 5 to 6(57 lp/mm). The USB camera's measured MTF matches the USAF cutofffrequency of group 3 to 6 (14.25 lp/mm).

FIG. 11 illustrates normalized luminance maps showing illuminationuniformity of each device and each illumination wavelength correspondingto U in Eq. (5)

The use of low-cost, compact, high-power, high-efficacy, surface mountLEDs improves on the costs and complexities associated with laser-based,interference-filter-based, and spectrometer-based dermascope systems.While these systems likely allow for better discrimination due to theirnarrow-bandwidth sources or detection schemes, the costs involved (withthe possible exception of the laser-based systems) are prohibitive.High-reliability LEDs are available in myriad wavelengths to probevarious points along the chromophore molar attenuation curves (FIG. 3 )and can be powered with simple driving circuits. Surface-mount packagesremove the bulk of transistor outline can packages (or larger packages)necessary for edge-emitting lasers, and the broad wavelength selectionis wider than that of surface mount laser packages such asvertical-cavity surface-emitting lasers. The cost of LED sourcescompared with laser sources or interference filters allows for the useof multiple wavelengths in a single system while keeping bill ofmaterials (BOM) costs low.

TABLE 3 LED illumination uniformity according to Eq. (21). WavelengthSmartphone camera USB camera White 0.954 0.880 450 0.974 0.980 470 0.9820.977 500 0.935 0.969 530 0.977 0.955 580 0.980 0.949 660 0.916 0.972810 0.852 0.900 940 0.907 0.870

TABLE 4 Measured CIEXYZ normalization constants for both dermascopes.Smartphone camera USB camera X_(n) 82.873 82.846 Y_(n) 100 100 Z_(n)34.567 48.757

In clinical testing, both systems (a smartphone camera based dermascopeand a USB camera based dermascope according to the present disclosure)were able to capture full image datasets and return similar results ofrelative chromophore concentrations across multiple dermal lesionsexcept for Hb in the JN case, as shown in FIGS. 6(a)-6(f). The deviationcould be explained by the difference in IR imaging performance betweenthe two dermascopes.

In addition, relative melanin content and erythema as measured throughthe CIELAB white-light images and OD color images agreed between thesystems and are reasonable based on visual examination. The USB cameraand smartphone camera have differing levels of luminance in theirwhite-light images as seen in FIGS. 6 and 7 , leading to a difference inbaseline lightness and redness values, where the higher luminancesmartphone images show higher overall L* and a* values. However, as seenin FIG. 6 , the relative changes are similar, where ΔL*≈3 between thenevus and surrounding skin and Δa*≈3 between the nevus and surroundingskin.

The occlusion test (FIG. 8 ) provided directionally correct results forboth dermascopes, although the magnitudes of change in chromophoreconcentration were dissimilar between dermascopes. Again, this deviationcould be explained by the difference in IR imaging performance betweenthe two dermascopes.

Once a large dataset reflecting multiple types of skin lesions inaddition to a wide range of baseline melanin levels in patients iscollected along with biopsy and diagnosis results, classificationalgorithms can be built using machine learning, principal componentsanalysis, or similar tools. The statistics of the large dataset and theclassifier can then be used to predict the relationships betweenchromophores, lesion type, and diagnosis. In our two datasets,high-melanin concentrations were present for the JN case but not for theSCC case. The classifier can help to determine if this relationship istrue more generally or how this might change in patients with highbaseline levels of melanin. Likewise, while the Hb and HbO₂ levels weresimilar in our two datasets, a larger dataset might reveal thatcancerous activity increases blood flow, increasing both Hb and HbO₂ andpossibly the ratios between them. The classifier could use additionalfeatures and relationships in the images. For example, by Eq. (12), theoptical path length increases as the wavelength increases, increasingthe probe depth. Detecting lesion shape changes over depth through edgedetection or similar means could provide another layer of information.Indications of these changes are apparent in both the JN and SCC casesas both have changing edges as the wavelength changes. Likewise, theclassifier could potentially use additional measures such as bloodcontrasts and oxygenation percentages.

Both cameras produced approximately linear responses when changingexposure time in the case of the smartphone camera dermascope andbrightness in the case of the USB camera dermascope, providingconfidence in the ability of the systems to have a linear response tointensity changes from illumination absorption.

For the smartphone dermascope, the measured MTF performance matched boththe predicted diffraction-limited performance and the cutoff frequencymeasured with the USAF target where group 5 to 6 (57 lp/mm) isresolvable. The root mean square error (RMSE) between the measured MTFand predicted diffraction-limited performance was RMSE=0.97. The USBdermascope's measured MTF performance did not match the predicteddiffraction-limited performance (RMSE=0.384); however, fullspecifications of the imaging lens are not provided by the manufacturer,precluding a more accurate estimation of the true diffraction-limitedperformance. The lens' NA was estimated to be 0.004 based on theslanted-edge measurement. The measured MTF cutoff frequency matched theUSAF target measurement where group 3 to 6 (14.25 lp/mm) was resolvable.As shown in the dermal images, both dermascopes demonstrated sufficientimage quality for most reasonably sized lesions, with the ability toresolve features as small as 17 μm for the smartphone dermascope and 70μm for the USB dermascope.

Illumination uniformity was greater than 85% for all wavelengths withboth dermascopes and was easily corrected in the image processingalgorithms.

In some embodiments, further improvements can be made by incorporatingcolor-to-color spatial image registration to reduce image blur at theborder markings. Increasing capture speed also reduces the likelihoodfor image blur between images, easing the need for color-to-color imageregistration while faster image capture would also increase patientcomfort. In systems where image capture speed is not able to beincreased, having added markings would likely improve registrationbecause they provide high contrast, well-defined features to extract.

In some embodiments where the portable electronic device has two (or ingeneral more than one) rear cameras, the mulitiple cameras can be usedto provide depth imaging and enable stereoscopic 3D imaging to provide atopography of the skin lesion. Alternatively, each of the multiplecameras could provide different FOVs or different NAs for imagingflexibility.

In some embodiments, additional illumination optics, such as diffusers,are used to increase illumination uniformity. The LED board wasoriginally designed to take advantage of the dual cameras of the LG G5,but reducing the center aperture of the LED board can increaseillumination uniformity and reduce system size. LED wavelengths can alsobe tailored to the task or expanded into UV wavelengths to probepotential autofluorescence signatures.

In an example use case, the smartphone-based dermascopes for dermallesion screening and erythema monitoring using PMSI and PWLI describedherein can augment the capabilities of PCPs, with the potential forearlier detection of melanoma and NMSC along with quantitativemonitoring of erythema. The combination of LED sources, 3D-printing, andsmartphone-based imaging enables the creation of low-cost (a high-volumeBOM cost of <$40 excluding the smartphone should be easily achievable),feature-rich, easy-to-use medical imaging devices using either asmartphone camera or a USB camera.

FIGS. 12-14 provide flowcharts to help visualize the processingalgorithms for the reference, white-light images, and color imagesprovided in Algorithms 1 and 2.

FIG. 12 show a flow diagram of an example embodiment of a method ofprocessing reference images according to Algorithm 1.

FIG. 13 show a flow diagram of an example embodiment of a method ofprocessing white-light images according to Algorithm 2.

FIG. 14 show a flow diagram of an example embodiment of a method ofprocessing multi spectral images according to Algorithm 2.

While the Hb and HbO₂ chromophore levels should change during the fingerocclusion test as shown in FIG. 8 , the melanin and background measuresshould remain constant. FIG. 15 shows the additional measures during theocclusion test. Here, the melanin measure has been divided by 100 andthe background measure divided by 10,000 for easier comparison ofchanges between measures. Here, the USB camera's melanin and backgroundmeasurements are more stable over the time points compared with thesmartphone camera.

FIG. 15 illustrates finger occlusion test results for the smartphonecamera and USB camera at pre-occlusion, after occlusion for 2 min, andpostocclusion for Hb, HbO₂, melanin, and background measures resultingfrom Eq. (14). Here, the melanin measure has been divided by 100 and thebackground measure divided by 10,000 for easier comparison with thechanges in Hb and HbO₂.

FIG. 16 shows a dermascope 1600 according to an example embodiment. Thedermascope illustrated in FIG. 16 includes internal mobile imagingsensor(s) 1610 and external imaging sensor(s) 1620 to capture imagesover the same region of the skin. Such configuration enables, amongother features and benefits, obtaining different information regardingskin properties based on the captured images. For example, with morethan one sensor imaging the same region sequentially, the images withdifferent skin properties can be correlated accurately for furtheranalysis. The configuration of FIG. 16 also overcomes the limitations ofthe internal mobile imaging sensor—i.e., typically a color sensor havinga short pass filter to block the light beyond 700 nm—by providing anexternal imaging sensor(s) that can be monochromatic and/or colorsensors but, e.g., without the short pass filter. With differentspectral filters, such as a long pass filter, a short pass filter, and aband pass filter, the monochromatic sensor can capture additional skinproperties, such as autofluorescence. By orienting a polarizer in frontof each sensor at different angles relative to the polarizer in front ofthe LEDs, more information on the skin polarization properties can beobtained as well. With two or more external sensors, 3D skin tomographycan also be obtained.

FIG. 17 shows a flow diagram of an example embodiment of a method 1700according to the disclosed technology. The method 1700 includes aprocess 1710 of illuminating an area of the skin using a plurality oflight sources having distinct spectral content to provide illuminationin a plurality of distinct wavelengths or range of wavelengths wheredeoxyhemoglobin, oxyhemoglobin, or melanin exhibit differing opticalcharacteristics. The method 1700 further includes a process 1720 ofobtaining one or more images of the area of the skin. The method 1700also includes a process 1730 of processing information associated withthe one or more images to obtain a level of at least one chromophore inthe skin.

FIG. 18 shows a set of operations 1800 for imaging an area of a skinfacilitate a determination of a skin condition in accordance with anexample embodiment. At 1810, an area of a skin is illuminated using aplurality of light sources having distinct spectral content to provideillumination in a plurality of distinct wavelengths or range ofwavelengths where the skin produces differing optical responses. At1820, one or more images of the area of the skin associated with theillumination in the plurality of distinct wavelengths or range ofwavelengths is obtained. At 1830, information associated with the one ormore images is processed to obtain a level of at least onecharacteristic that is associated with the skin condition. In oneexample embodiment, the differing optical responses include responsesthat are based on differing optical characteristics of deoxyhemoglobin,oxyhemoglobin, or melanin in response to illumination in the pluralityof distinct wavelengths or range of wavelengths, and the processingproduces the level of at least one chromophore in the skin.

An aspect of the disclosed embodiments relates to a dermascope forimaging an area of a skin, comprising: a plurality of light sourceshaving different spectral contents and configured to illuminate the areaof the skin; at least one imaging sensor configured to collect images ofthe area of the skin; a processor and a memory comprising instructionsstored thereon, wherein the instructions upon execution by theprocessor, cause the processor to: control illumination provided by theplurality of light sources to the area of the skin, and processinformation associated with the images produced from reflected lightfrom the area of the skin to enable detection of a level of one or morechromophores in the skin, wherein illumination from the plurality oflight sources is controlled to provide illumination in a plurality ofdistinct wavelengths or range of wavelengths where the one or morechromophores exhibit differing optical characteristics.

In some example embodiments of the dermascope, the processor isconfigured to determine an optical density value associated with two ormore of the plurality of distinct wavelength. According to some exampleembodiments, the processor is configured to determined one or botherythema or melanin based on the determined optical density values. Inan example embodiment, the plurality of distinct wavelengths or range ofwavelengths is selected to include two or more wavelengths at which atleast two chromophores exhibit differing extinction coefficients. Inanother example embodiment, at a first of the two or more wavelengths, afirst of the at least two chromophores has a higher molar extinctioncoefficient than a second of the at least two chromophores, at a secondof the two or more wavelengths, the first of the at least twochromophores has a lower molar extinction coefficient than the second ofthe at least two chromophores. In some example embodiments, at a thirdwavelength, the first and the second of the at least two chromophoreshave substantially similar molar extinction coefficients.

According to some example embodiments, the two or more wavelengths atwhich the at least two chromophores exhibit differing extinctioncoefficients correspond to two or more wavelengths at which that atleast two chromophores exhibit two or more largest differences in theirextinction coefficients. In some example embodiments, the chromophoresinclude one or more of deoxyhemoglobin, oxyhemoglobin, or melanin. In anexample embodiment, the plurality of light sources includes a whitelight source. In some example embodiments, the dermascope comprises anillumination polarizer configured to receive light from the plurality oflight sources and transmit therethrough light having a firstpolarization state towards the skin. According to some exampleembodiments, the illumination polarizer is one of a linear polarizer ora circular polarizer. In an example embodiment, the dermascope comprisesan imaging polarizer configured to receive light from the skin.

According to an example embodiment, the processor is configured tocontrol illumination intensity of at least one light source in theplurality of light sources. In some example embodiments, the dermascopecomprises multiple light sources having substantially the same spectralillumination characteristics, wherein the processor is configured tocontrol the illumination by controlling output illumination of themultiple light sources individually or collectively. According to someexample embodiments, the dermascope is implemented as part of a mobileelectronic device. In certain example embodiments, the mobile electronicdevice is mobile phone or a tablet. In some example embodiments, thedermascope is implemented as part of a mobile electronic device thatincludes a camera lens, and the dermascope further includes an auxiliaryoptical system configured to be positioned in front of the mobileelectronic device's camera lens or configured as a separate componentthat is in communication with the mobile electronic device. Theauxiliary optical system includes one or more optical components toproduce one or more of a particular: numerical aperture, field of view,spectral response or optical zoom capability for the dermascope.According to some example embodiments, the auxiliary optical systemincludes an achromatic doublet. In some example embodiments, thedermascope includes an auxiliary optical system configured to operatewith a mobile electronic device and a portion of the dermascope thatincludes the at least one imaging sensor, the auxiliary optical systemand the plurality of light sources is configured as a separate componentfrom the mobile electronic device that is operable for positioningagainst the area of the skin, the separate component being incommunication with the electronic mobile device, and the processor andthe memory are integral parts of the mobile electronic device.

In an example embodiment, the dermascope includes an auxiliary opticalsystem configured to operate with a mobile electronic device, and aportion of the dermascope that includes the auxiliary optical system andthe plurality of light sources is configured as an attachable componentto the mobile electronic device, and one of the at least one imagingsensor, the processor and the memory are integral parts of the mobileelectronic device, wherein the attachable component is configured toattach to the electronic mobile device in such a way as to position theauxiliary optical system in front of, and in alignment with, the imagingsensor of the electronic mobile device. In another example embodiment,the dermascope includes an auxiliary optical system configured tooperate with a mobile electronic device, a portion of the dermascopethat includes the auxiliary optical system that includes a first one ofthe at least one imaging sensor is configured as an attachable componentto the mobile electronic device, and a second one of the at least oneimaging sensor, the processor and the memory are integral parts of themobile electronic device. The attachable component can be configured toattach to the electronic mobile device in such a way as to position theauxiliary optical system in front of, and in alignment with, the secondone of the at least one imaging sensor.

According to an example embodiment, the dermascope comprises an imagingannulus as part of the separate or the attachable component, the annulushaving a side wall between a first end and a second end and forming ahollow interior between the first end and the second end, wherein theplurality of light sources and the imaging sensor are positionedproximate to the first end of the imaging annulus and the second end ofthe imaging annulus is adapted to be positioned against the skin suchthat when the imaging annulus is in contact with the skin, illuminationof the area of the skin is predominantly due to the light produced bythe plurality of light sources. One or both or the first or the secondends of the annulus can be open. In another example embodiment, theimaging annulus includes a transparent material that is positionedproximate to the second end of the imaging annulus to allow the annulusto be pressed against the skin and to thereby produce a substantiallyflat object plane. In some example embodiments, the imaging sensorincludes two or more cameras that are configured to obtain images fromthe area of skin. According to some example embodiments, the processoris configured to produce one of more of the following based on imagesobtained from the two or more cameras: depth imaging information,autofluorescence information, three-dimensional images, images withdiffering resolution or images with differing magnifications. In certainexample embodiments, the dermascope comprises one or more spectralfilters to allow light of a particular spectral content to reach one ormore of the cameras. In some example embodiments, the one or morefilters include a long pass filter, a short pass filter, or a band passfilter. In an example embodiment, the dermascope comprises threecameras. In an example embodiment of the dermascope, one of theplurality of light sources is operable to emit radiation in an infraredrange of wavelengths. According to an example embodiment, one of theplurality of light sources is operable to emit radiation in anultraviolet range of wavelengths.

Another aspect of the disclosed embodiments relates to a method ofimaging an area of a skin to determine a content of at least onechromophore in the skin, comprising: illuminating the area of the skinusing a plurality of light sources having distinct spectral content toprovide illumination in a plurality of distinct wavelengths or range ofwavelengths where deoxyhemoglobin, oxyhemoglobin, or melanin exhibitdiffering optical characteristics; obtaining one or more images of thearea of the skin; and processing information associated with the one ormore images to obtain a level of at least one chromophore in the skin.

In some example embodiments of the method, processing the informationcomprises determining optical density values associated with two or moreillumination wavelengths to quantify erythema. According to some exampleembodiments, the method further comprises converting a white-light imageof the area of the skin into CIELAB color space and performing one orboth of the following: (a) using lightness, L* to determine a relativemeasure of melanin content, or (b) using a direction of red colorstimuli, a* as a measure of redness, wherein more positive values of thered color stimuli are indicative of higher levels of erythema.

Another aspect of the disclosed embodiments relates to a dermascope forimaging an area of a skin that incudes a plurality of light sourceshaving different spectral contents and configured to illuminate the areaof the skin, and at least one imaging sensor configured to detect lightreceived from the area of the skin that is illuminated by the pluralityof light sources. The dermascope further includes a processor and amemory comprising instructions stored thereon, wherein the instructionsupon execution by the processor, cause the processor to: controlillumination provided by the plurality of light sources to the area ofthe skin, and

-   -   process information associated with the light detected by the at        least one imaging sensor to produce images of the area of the        skin. The illumination from the plurality of light sources is        controlled to provide illumination in a plurality of distinct        wavelengths or range of wavelengths that produce differing        optical responses of the area of the skin. In one example        embodiment, the produced images enable detection of a level of        one or more chromophores in the skin, and the plurality of        distinct wavelengths or range of wavelengths is selected to        include two or more wavelengths at which at least two        chromophores exhibit differing extinction coefficients.

While this patent document contains many specifics, these should not beconstrued as limitations on the scope of any invention or of what may beclaimed, but rather as descriptions of features that may be specific toparticular embodiments of particular inventions. Certain features thatare described in this patent document in the context of separateembodiments can also be implemented in combination in a singleembodiment. Conversely, various features that are described in thecontext of a single embodiment can also be implemented in multipleembodiments separately or in any suitable subcombination. Moreover,although features may be described above as acting in certaincombinations and even initially claimed as such, one or more featuresfrom a claimed combination can in some cases be excised from thecombination, and the claimed combination may be directed to asubcombination or variation of a sub combination.

Similarly, while operations are depicted in the drawings in a particularorder, this should not be understood as requiring that such operationsbe performed in the particular order shown or in sequential order, orthat all illustrated operations be performed, to achieve desirableresults. Moreover, the separation of various system components in theembodiments described in this patent document should not be understoodas requiring such separation in all embodiments.

It is understood that the various disclosed embodiments may beimplemented individually, or collectively, in devices comprised ofvarious optical components, electronics hardware and/or software modulesand components. These devices, for example, may comprise a processor, amemory unit, an interface that are communicatively connected to eachother, and may range from desktop and/or laptop computers, to mobiledevices and the like. The processor and/or controller can performvarious disclosed operations based on execution of program code that isstored on a storage medium. The processor and/or controller can, forexample, be in communication with at least one memory and with at leastone communication unit that enables the exchange of data andinformation, directly or indirectly, through the communication link withother entities, devices and networks. The communication unit may providewired and/or wireless communication capabilities in accordance with oneor more communication protocols, and therefore it may comprise theproper transmitter/receiver antennas, circuitry and ports, as well asthe encoding/decoding capabilities that may be necessary for propertransmission and/or reception of data and other information. Forexample, the processor may be configured to receive electrical signalsor information from the disclosed sensors (e.g., CMOS sensors), and toprocess the received information to produce images or other informationof interest.

Various information and data processing operations described herein maybe implemented in one embodiment by a computer program product, embodiedin a computer-readable medium, including computer-executableinstructions, such as program code, executed by computers in networkedenvironments. A computer-readable medium may include removable andnon-removable storage devices including, but not limited to, Read OnlyMemory (ROM), Random Access Memory (RAM), compact discs (CDs), digitalversatile discs (DVD), etc. Therefore, the computer-readable media thatis described in the present application comprises non-transitory storagemedia. Generally, program modules may include routines, programs,objects, components, data structures, etc. that perform particular tasksor implement particular abstract data types. Computer-executableinstructions, associated data structures, and program modules representexamples of program code for executing steps of the methods disclosedherein. The particular sequence of such executable instructions orassociated data structures represents examples of corresponding acts forimplementing the functions described in such steps or processes

Only a few implementations and examples are described and otherimplementations, enhancements and variations can be made based on whatis described and illustrated in this patent document.

Algorithm 1 Processing of reference images.  1: procedureProcessReferenceImages (reference images)  2:  for all reference imagesdo  3:     convert sRGB to linear RGB

 Eq. (1)  4:     if white-light image then  5:       convert linear RGBto CIEXYZ

 Eq. (2)  6:     else if color image then  7:       convert linear RGBto Yequal

 Eq. (3)  8:     end if  9:     calculate luminance reference

 Eq. (4) 10:      calculate illumination uniformity reference

 Eq. (5) 11:    end for 12:    return optical density reference images13:    return illumination uniformity images 14:  end procedure

Algorithm 2 Processing of dermal images.  1: procedureProcessDermalImages (dermal images)  2:   for all dermal images do  3:    If USB camera then  4:       correct white-light image luminance   

 Eq. (8)  5:   end if  6:   convert sRGB to linear RGB   

 Eq. (1)  7:   correct by illumination uniformity   

 Eq. (6)  8:   if white-light image then  9:     convert linearRGB toCIEXYZ   

 Eq. (2) 10:      convert CIEXYZ to CIELAB

 Eqs. (17) and (18) 11:    else if color image then 12:      convertlinear RGB to Yequal   

 Eq. (3) 13:      calculate optical density   

 Eq. (7) 14:      calculate melanin content  

 Eq. (19) 15:      calculate erythema  

 Eq. (20) 16:      solve chromophore concentration  

 Eq. (14) 17:      end if 18:    end for 19:  end procedure

1. A dermascope for imaging an area of a skin, comprising: a pluralityof light sources having different spectral contents and configured toilluminate the area of the skin; at least one imaging sensor configuredto detect light received from the area of the skin that is illuminatedby the plurality of light sources; a processor and a memory comprisinginstructions stored thereon, wherein the instructions upon execution bythe processor, cause the processor to: control illumination provided bythe plurality of light sources to the area of the skin, and processinformation associated with the light detected by the at least oneimaging sensor to produce images of the area of the skin, whereinillumination from the plurality of light sources is controlled toprovide illumination in a plurality of distinct wavelengths or range ofwavelengths that produce differing optical responses of the area of theskin.
 2. The dermascope of claim 1, wherein the processor is configuredto determine an optical density value associated with two or more of theplurality of distinct wavelength.
 3. (canceled)
 4. The dermascope ofclaim 1, wherein: the produced images enable detection of a level of oneor more chromophores in the skin, the plurality of distinct wavelengthsor range of wavelengths is selected to include two or more wavelengthsat which at least two chromophores exhibit differing extinctioncoefficients, at a first of the two or more wavelengths, a first of theat least two chromophores has a higher molar extinction coefficient thana second of the at least two chromophores, and at a second of the two ormore wavelengths, the first of the at least two chromophores has a lowermolar extinction coefficient than the second of the at least twochromophores.
 5. (canceled)
 6. The dermascope of claim 4, wherein at athird wavelength, the first and the second of the at least twochromophores have substantially similar molar extinction coefficients.7. The dermascope of claim 4, wherein the two or more wavelengths atwhich the at least two chromophores exhibit differing extinctioncoefficients correspond to two or more wavelengths at which that atleast two chromophores exhibit two or more largest differences in theirextinction coefficients.
 8. The dermascope of any of claims 4, whereinthe chromophores include one or more of deoxyhemoglobin, oxyhemoglobin,or melanin.
 9. The dermascope of claim 1, wherein the plurality of lightsources includes a white light source.
 10. The dermascope of claim 1,comprising an illumination polarizer configured to receive light fromthe plurality of light sources and transmit therethrough light having afirst polarization state towards the skin, and an imaging polarizerconfigured to receive light from the skin.
 11. (canceled)
 12. (canceled)13. The dermascope of claim 1, wherein the processor is configured tocontrol illumination intensity of at least one light source in theplurality of light sources.
 14. The dermascope of claim 1, comprisingmultiple light sources having substantially the same spectralillumination characteristics, wherein the processor is configured tocontrol the illumination by controlling output illumination of themultiple light sources individually or collectively.
 15. (canceled) 16.(canceled)
 17. The dermascope of claim 1, wherein the dermascope isimplemented as part of a mobile electronic device that includes a cameralens, and the dermascope further includes an auxiliary optical systemconfigured to be positioned in front of the mobile electronic device'scamera lens or configured as a separate component that is incommunication with the mobile electronic device, the auxiliary opticalsystem including one or more optical components to produce one or moreof a particular: numerical aperture, field of view, spectral response,or optical zoom capability for the dermascope.
 18. The dermascope ofclaim 17, wherein the auxiliary optical system includes an achromaticdoublet.
 19. The dermascope of claim 1, wherein the dermascope includesan auxiliary optical system configured to operate with a mobileelectronic device, a portion of the dermascope that includes one of theat least one imaging sensor, the auxiliary optical system and theplurality of light sources is configured as a separate component fromthe mobile electronic device that is operable for positioning againstthe area of the skin, the separate component being in communication withthe electronic mobile device, and the processor and the memory areintegral parts of the mobile electronic device.
 20. The dermascope ofclaim 1, wherein the dermascope includes an auxiliary optical systemconfigured to operate with a mobile electronic device, a portion of thedermascope that includes the auxiliary optical system and the pluralityof light sources is configured as an attachable component to the mobileelectronic device, and one of the at least one imaging sensor, theprocessor and the memory are integral parts of the mobile electronicdevice, wherein the attachable component is configured to attach to theelectronic mobile device in such a way as to position the auxiliaryoptical system in front of, and in alignment with, the imaging sensor ofthe electronic mobile device.
 21. The dermascope of claim 1, wherein thedermascope includes an auxiliary optical system configured to operatewith a mobile electronic device, a portion of the dermascope thatincludes the auxiliary optical system includes a first one of the atleast one imaging sensor, and is configured as an attachable componentto the mobile electronic device, and a second one of the at least oneimaging sensor, the processor and the memory are integral parts of themobile electronic device, wherein the attachable component is configuredto attach to the electronic mobile device in such a way as to positionthe auxiliary optical system in front of, and in alignment with, thesecond one of the at least one imaging sensor.
 22. The dermascope ofclaim 19, comprising an imaging annulus as part of the separate or theattachable component, the annulus having a side wall between a first endand a second end and forming a hollow interior between the first end andthe second end, wherein the plurality of light sources and one of the atleast one imaging sensor are positioned proximate to the first end ofthe imaging annulus and the second end of the imaging annulus is adaptedto be positioned against the skin such that when the imaging annulus isin contact with the skin, illumination of the area of the skin ispredominantly due to the light produced by the plurality of lightsources.
 23. The dermascope of claim 22, wherein the imaging annulusincludes a transparent material that is positioned proximate to thesecond end of the imaging annulus to allow the annulus to be pressedagainst the skin and to thereby produce a substantially flat objectplane.
 24. The dermascope of claim 1, wherein the at least one imagingsensor includes two or more imaging sensors that are configured toobtain images from the area of skin, and wherein the processor isconfigured to produce one of more of the following based on imagesobtained from the two or more imaging sensors: depth imaginginformation, autofluorescence information, three-dimensional images,images with differing resolution or images with differingmagnifications.
 25. (canceled)
 26. The dermascope of claim 1, comprisingone or more spectral filters to allow light of a particular spectralcontent to reach one or more of the at least one imaging sensor, whereinthe one or more filters include a long pass filter, a short pass filter,or a band pass filter.
 27. (canceled)
 28. The dermascope of claim 1,wherein at least one of the plurality of light sources is operable toemit radiation in an infrared range of wavelengths, or in an ultravioletrange of wavelengths.
 29. (canceled)
 30. A method of imaging an area ofa skin facilitate a determination of a skin condition , comprising:illuminating an area of a skin using a plurality of light sources havingdistinct spectral content to provide illumination in a plurality ofdistinct wavelengths or range of wavelengths where the skin producesdiffering optical responses; obtaining one or more images of the area ofthe skin associated with the illumination in the plurality of distinctwavelengths or range of wavelengths; and processing informationassociated with the one or more images to obtain a level of at least onecharacteristic that is associated with the skin condition.
 31. Themethod of claim 30, wherein the differing optical responses includeresponses that are based on differing optical characteristics ofdeoxyhemoglobin, oxyhemoglobin, or melanin in response to illuminationin a plurality of distinct wavelengths or range of wavelengths, and theprocessing produces the level of at least one chromophore in the skin.32. The method of claim 30, wherein processing the information comprisesdetermining optical density values associated with two or moreillumination wavelengths to quantify erythema.
 33. The method of claim30, comprising converting a white-light image of the area of the skininto CIELAB color space and performing one or both of the following: (a)using lightness, L* to determine a relative measure of melanin content,or (b) using a direction of red color stimuli, a* as a measure ofredness, wherein more positive values of the red color stimuli areindicative of higher levels of erythema.